🧪Endocrinology🧪 - Disorders of Vasopressin

Question 1

What is the pathway of AVP release?

Answer 1

Supraoptic hypothalamic nuclei -> pituitary stalk -> posterior pituitary
Originates in magnocellular neurones

Question 2

What is the other name for arginine vasopressin (AVP)?

Answer 2

Anti-diuretic hormone (ADH)

Question 3

What is diuresis?

Answer 3

The production of urine

Question 4

What is the main physiological action of AVP?

Answer 4

Stimulation of water reabsorption in the renal collecting duct, via V2 receptors
Concentrates urine, increases blood volume

Question 5

What are 2 physiological effects of AVP, other than stimulating water reabsorption?

Answer 5

Acts as a vasoconstrictor, via the V1 receptor
Stimulates ACTH release from anterior pituitary (much smaller impact than CRH obviously)

Question 6

Describe the chemical cascade after AVP binds to its target

Answer 6

AVP binds to g-protein coupled v2 receptor
Causes adenylate cyclase to form cAMP
cAMP then forms protein kinase A
Protein kinase A interacts with vesicles containing aquaporin-2
Aquaporin-2 channels insert into the apical membrane, leading to water movement into the cell

Question 7

What receptors are responsible for the release of AVP?

Answer 7

Osmoreceptors

Question 8

What triggers osmoreceptors?

Answer 8

Increase in plasma osmolality is sensed

Question 9

Where are osmoreceptors located?

Answer 9

The hypothalamus

Question 10

How do osmoreceptors regulate AVP release?

Answer 10

Question 11

What is the normal physiological response to water deprivation?

Answer 11

Question 12

What are the 2 types of conditions relating to the inefficacy of AVP?

Answer 12

Arginine vasopressin deficiency (AVP-D)
Arginine vasopressin resistance (AVP-R)

Question 13

Outline AVP-D

Answer 13

Cranial (central) diabetes insipidus
Problem with the hypothalamus and/or posterior pituitary
Inability to properly produce AVP

Question 14

Outline AVP-R

Answer 14

Nephrogenic diabetes insipidus
AVP production is fine
Kidney (collecting duct) unable to respond
Is insensitivity to AVP

Question 15

How does AVP deficiency/resistance present?

Answer 15

Question 16

How can AVP deficiency lead to death?

Answer 16

Restricted access to water leads to rapid dehydration and death

Question 17

What is the clinical presentation of AVP deficiency/resistance?(4)

Answer 17

Polyuria
Nocturia
Thirst - often extreme
Polydipsia

Question 18

A patient presents with polyuria, nocturia and polydipsia, what is the most common cause?

Answer 18

Diabetes MELLITUS

Question 19

Why is diabetes mellitus always considered first, before a problem with vasopressin?

Answer 19

Because the symptoms present the same/very similarly upon first presentation, and diabetes mellitus is much more common

Question 20

What is the most common cause of AVP deficiency, and how may it arise?

Answer 20

Acquired
Traumatic brain injury
Pituitary surgery
Pituitary tumours
Inflammation of pituitary stalk (e.g. TB)
Autoimmune damage
Congenital is rare

Question 21

What are the causes of AVP resistance?

Answer 21

Much less common than AVP deficiency
Acquired - via drugs (e.g. lithium)
Congenital - rare (mutation in gene encoding for V2 receptor)

Question 22

What would the urine of someone with AVP issues be like?

Answer 22

Very dilute - hypo-osmolar
Large volume

Question 23

What would the blood plasma of someone with diabetes insipidus look like, and how could it be distinguished from diabetes mellitus?

Answer 23

Increased concentration (hyperosmolar)
Hypernatraemia
Normal glucose (used to distinguish from DM)

Question 24

What condition other than diabetes mellitus can mimic AVP deficiency?

Answer 24

Psychogenic polydipsia

Question 25

What is psychogenic polydipsia?

Answer 25

A patient **drinks vast amounts of water**, so passes h**uge volumes of urine**, and this can lead to **low plasma osmolality, and hyponatraemia** **Entirely psychological**

Question 26

How might someone with psychogenic polydipsia present?

Answer 26

Polydipsia Polyuria Nocturia

Question 27

How do the symptoms arise in psychogenic polydipsia?

Answer 27

**Increased water intake** leads to **increased blood volume** and **filtration in kidneys** **Plasma osmolality falls, including sodium levels** **Less AVP secreted** by posterior pituitary, to discourage water reabsorption and so **increase urine volume** Large volumes of **dilute, hypotonic urine** Plasma osmolality returns to normal

Question 28

How is AVP deficiency distinguished from psychogenic polydipsia?

Answer 28

**Water deprivation test** No access to any fluid intake Over time measures of: -Urine volumes -Urine osmolality -Plasma osmolality

Question 29

What must also be carefully monitored during the water deprivation test?

Answer 29

Body weight **Test should be stopped if more than 3% of body weight is lost** - a marker of significant dehydration

Question 30

What will the results of the water deprivation test look like for psychogenic polydipsia and AVP deficiency?

Answer 30

Question 31

Why does psychogenic polydipsia show a lower level of water reabsorption than the normal person during the water deprivation test?

Answer 31

(*Depends on severity and duration of the condition)* over time the **kidney loses ability to concentrate urine as effectively**, so less water reabsorption Urine concentration will **eventually match that of "normal" graph**, but takes more time

Question 32

How do we distinguish between AVP deficiency and AVP resistance?

Answer 32

**Give desmopressin** AVP **deficiency** will give a **positive response** AVP **resistance** will give **no response** as **kidneys cant respond**

Question 33

How is AVP-deficiency treated?

Answer 33

Replaced vasopressin **Desmopressin** commonly used Selective for V2 receptor Comes in **tablet and intranasal forms**, recently more **push towards the tablet form**

Question 34

How is AVP-resistance treated?

Answer 34

**Very difficult to treat** successfully, luckily is **very rare** **Symptom management** - low sodium diet and adequate hydration

Question 35

What is Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)?

Answer 35

**Too much arginine vasopressin**secretion Leads to **reduced urine output and urine retention**

Question 36

What are the physiological changes brought on by SIADH?

Answer 36

High urine osmolality Low plasma osmolality Low plasma sodium (dilute)

Question 37

What are some causes of SIADH?

Answer 37

**CNS** - head injury, stroke tumour **Lung infections** - pneumonia **Malignancy** - Lung cancer *(small cell*) **Drug related** - anti-epileptics, anti-depressants **Idiopathic**

Question 38

How is SIADH managed?

Answer 38

**Fluid restriction** Can use a **vasopressin receptor antagonist** (*vaptan*) - binds to the V2 receptors in the kidney, preventing activation - **very expensive**